Anhydro sugar alcohols, in particular derivatives of mannitol, iditol, and sorbitol, are known for their therapeutic uses and uses in food. At least one of these, isosorbide, 1,4:3,6-dianhydrosorbitol, is useful as a monomer used in the manufacture of polymers and copolymers, especially polyester polymers and copolymers.
Anhydro sugar alcohols are produced by dehydration of the corresponding sugar alcohols (or monoanhydro sugar alcohols) by the action of various dehydration catalysts, typically strong acid catalysts. Examples of these catalysts include sulfonated polystyrenes (H+ form) and various mineral acids, such as HCl, H3PO4, HF and H2SO4.
Batch processes for the preparation of dianhydro sugar alcohols by acid dehydration have been described in the prior art.
In particular, a batch process for the formation of the dianhydro sugar alcohol isosorbide has been described as a two-step process involving intramolecular dehydration of sorbitol to sorbitan (1,4-monoanhydrosorbitol), and further reaction of sorbitan to isosorbide (1,4:3,6-dianhydrosorbitol) in an acid catalyzed dehydration-cyclization. In this process, an aqueous solution of sorbitol is charged to a batch reactor. The temperature is increased to 130° C.-135° C. under vacuum (35 mm Hg) to remove the water. When the sorbitol melt is free of water, a catalyst, usually sulfuric acid, is added and the temperature and vacuum levels are maintained. The operable temperature range of the reaction is very narrow. Higher temperatures lead to decomposition and charring of the end product, while lower temperatures inhibit the reaction rate due to difficulties in removal of the water of reaction. This reaction produces isosorbide and a higher molecular weight byproduct. The byproduct is presumably produced by water elimination between two or more sorbitol molecules, but its exact nature is not clearly defined. See G. Flèche and M. Huchette, Starch/Starke (1986), 38(c), 26-30 and Roland Beck, Pharm. Mfg Inc. (1996), 97-100. Other monoanhydro byproducts, 2,5-anhydro-L-iditol and 2,5-anhydro-D-mannitol, are also known to be produced under some reaction conditions (Acta. Chem. Scand. B 35, 441-449 (1981)).
For isosorbide to be used as a monomer in high volume polymers and copolymers, for applications such as containers, it needs to be produced in large quantities, preferably in a continuous process.
WO 00/14081 describes a continuous process for producing anhydro sugar alcohols, especially isosorbide, comprising the steps of introducing at least one sugar alcohol or monoanhydro sugar alcohol into a reaction vessel; dehydrating the sugar alcohol or monoanhydro sugar alcohol in the presence of an acid catalyst and an organic solvent to form a reaction product which is at least partly soluble in the organic solvent; removing water from the reaction vessel; removing organic solvent comprising the dissolved reaction product from the reaction vessel; separating the reaction product from the removed organic solvent; and recycling the organic solvent into the reaction vessel. The large amounts of organic solvent required for such a process make it economically and environmentally undesirable.
U.S. Pat. No. 6,407,266 describes a continuous process in which a process stream containing at least one sugar alcohol or monoanhydro sugar alcohol and, optionally, water is introduced to the first stage of a multistage reactor and then intimately contacted with a countercurrent flow of an inert gas at elevated temperature. This inert gas removes the bulk of any water present in the process stream. This dewatered process stream is then intimately contacted with a dehydration catalyst, with a counter current flow of an inert gas at elevated temperatures to remove water of reaction as formed. Finally, the product is removed from the bottom of the reactor.
The reaction product obtained by processes such as the above, contains about 70 to 80% by weight isosorbide and 20 to 30% undesired reaction byproducts. The reaction product thus needs to be subjected to one or more separation steps, such as evaporation, distillation or chromatographic separation, to isolate the isosorbide. Chromatographic separation is disclosed in U.S. Patent Application No. 60/246038 (filed 6, Nov. 2000). Separation by vaporization or distillation is difficult because of the low vapor pressure of isosorbide. For example, we have found that at 140° C., the vapor pressure is only 1.75 mm Hg. Evaporation or distillation at temperatures not much higher than about 140° C. is desirable to-minimize product degradation and obtain good purity isosorbide, but the recovery is poor. At higher temperatures, e.g., 170° C., more isosorbide is recovered, but it is of poorer quality.
U.S. Pat. No. 4,564,692 discloses a process using crystallization from aqueous solutions:to obtain the high purity needed for applications as polyol components in polyester and polyurethane polymers.
Commonly owned U.S. application Ser. No. 10/414,611, filed simultaneously herewith, discloses a combined reaction-separation process wherein dianhydro sugar alcohols are obtained as vapors in a stream of water vapor. The vapor streams from such a process are condensed, and the isosorbide needs further purification to obtain the high level of purity required for use in polymers such as polyesters, that is, at least 99.8% pure.
Commonly owned U.S. application Ser. No. 10/414,606, filed simultaneously herewith, provides an effective means of recovering and purifying dianhydro sugar alcohols from aqueous vapor strams, wherein purification by crystallization occurs while recovering the product by condensation, and a separate crystallization step is eliminated.
Commonly owned U.S. application Ser. No. 10/414,605, filed simultaneously herewith, provides a process wherein the reaction byproducts and dianhydro sugar alcohols not recovered initially from the reaction mass are recycled back to the reaction step and overall yield of the dianhydro sugar alcohols, such as isosorbide, is increased.
There is a need for an effective, integrated process to conduct the dehydration reaction and separation in a single, multistage reaction vessel; recover the product directly from the vapor stream as purified crystals; and recycle reaction byproducts so as to increase overall process yield. The object of the present invention is to provide such an effective, integrated process suitable for continuous, large-scale production of high purity, polymer grade dianhydro sugar alcohols in high yield.